For sensory science in general, a major goal is to understand the relationships among perceptions and the underlying sensory mechanisms at various levels; that is, to assign psychological consequences to the functions of the genes associated with the sensory system. Within bitter taste alone, there are dozens, of genes specifically involved just with detecting bitterness The daunting task of ascribing function to these genes will require a multidisciplinary approach that combines genetics and genomics with studies of perception and physiology. The ultimate long-term goal of the proposed project is to identify genes associated with specific bitter-taste sensitivities. An essential initial step towards the goals, as outlined in this proposal, is to phenotype bitter taste perception and to rigorously establish reliable individual differences. Subjects will be screened using a broad array of forced-choice and scaling techniques that examine many bitter perceptual attributes. We have now identified two robust classes of individual differences in bitterness sensitivities: (i) people who show a specific bitter insensitivity for sucrose octaacetate (SOA) and (ii) people who are totally bitter blind with otherwise normal taste. Bitter blindness is a rare trait found in three individuals thus far. SOA insensitivity appears in approximately 30% the population at large. In the present proposal, we will psychophysically screen approximately 500 subjects to identify affected SOA-insensitive probands and age, gender and race matched unaffected controls. The extended families of identified SOA-insensitive probands will be examined. Relative risk ratios, family correlations, segregation analyses and environmental and medical history interviews will be conducted to determine the heritability and, if genetic, the mode of inheritance for SOA insensitivity. The SOA study also has the advantage of examining a human phenotype that parallels the well-characterized mouse SOA insensitivity phenotype. DNA samples will be collected from all subjects, with the intention that candidate genes will be screened for polymorphisms and family-based linkage analysis conducted on a candidate region of the genome. As a second goal, 5000 subjects will be screened to determine the prevalence of bitter blindness. This novel phenotype will require extensive analysis in order to understand its impact on the perceptual taste world of affected individuals. Bitter blind probands and age, race and gender matched normal controls will be phenotyped psychophysically in' greater detail in the laboratory. The analyses of these important taste traits have the potential to reveal principles of organization of taste coding as well as underlying taste genomics.